Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Re: _|ANTIVIRAL RESISTANCE BAFFLES SCIENTISTS|_
Influenza Activity in Europe
During week 10 2008, the majority of European countries reported decreasing activity. Widespread influenza activity was reported in eight countries, regional activity in one country (Germany), local activity in six countries,
sporadic activity in 13 countries and no activity was reported in Wales. Influenza virus type B accounted for 63% of the total positive specimens collected during week 10 2008; however the majority of virus detections since the start of the season were influenza A (H1N1) viruses. Based on (sub)typing data of all influenza virus detections this season (N=13278; sentinel and non-sentinel data), 4871 (37%) were influenza A (unsubtyped), 4305 (32%) were A (H1), 121 (1%) were A (H3) and 3981 (30%) were B.
Based on the antigenic and/or genetic characterisation of 2913 influenza viruses, 60 were A/New Caledonia/20/99 (H1N1)-like, 1993 were A/Solomon Island/3/2006 (H1N1)-like, 17 were A/Wisconsin/67/2005 (H3N2)-like, 55 were A/Brisbane/10/2007 (H3N2)-like, 774 were B/Florida/4/2006-like (B/Yamagata/16/88 lineage) and 14 were B/Malaysia/2506/2004-like (B/Victoria/2/87 lineage).
Despite the mismatch of the circulating influenza B viruses with the vaccine strain, it is expected that the 2007/2008 vaccine still provides valuable protection due to cross reactive antibodies induced by the vaccine. A
number of recent A (H1N1) viruses are distinguishable from the vaccine virus in antigenic analyses. <b>As these viruses show better antigenic match to A/Brisbane/59/2007, the WHO has recommended that an A/Brisbane/59/2007-like virus is included in the vaccine for the 2008/2009 season. As there is still significant antigenic similarity, the present vaccine is expected to provide protection against the current H1N1 viruses.</b>
Influenza Weekly Surveillance Report
Week 11 2008 (10th? 16th March 2008)
A REPORT BY THE HEALTH PROTECTION SURVEILLANCE CENTRE
THE NATIONAL VIRUS REFERENCE LABORATORY &
THE DEPARTMENTS OF PUBLIC HEALTH
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Caught this on an internet search, posted 2002 meeting presentation slides.
http://images.medscape.com/pi/editorial/cmecircle/2002/1840/zangwill/slide11.gif
Influenza Viruses Resistant to Oseltamivir and Representing Three Distinct NA Genotypes Isolated by Hoffmann LaRoche from Clinical Studies Employing Oseltamivir as Treatment
Yes+, especially at lower infectious doses
H274Y ? interact with functional (histidine to tyrosine)
Only oseltamivir
A/New Caledonia/99
(H1N1)
[A/Texas/36/91-like]
Yes+, instability of NA but not enzyme activities
^E119V ? framework
(glutamic acid to valine)
Only oseltamivir
A/Wuhan/359/95-like
(H3N2)
Yes+ , serious effect on NA activity
*R292K ? functional
(arginine to lysine)
Both oseltamivir and zanamivir
A/Sydney/5/97-like
(H3N2)
Neuraminidase Inhibitor-Resistant Influenza Viruses May Differ Substantially in Fitness and Transmissibility. Webster et al. Antimicrob Agents Chemother. 2005 49(10):4075?4084.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1251536
Several studies in animal models have examined the infectivity of NAI-resistant viruses with mutations at the conserved NA residues. These viruses exhibited reduced virulence in mice and ferrets (3, 14, 19, 33). However, A/Wuhan/359/95-like (H3N2) virus with the E119V NA mutation was recently reported to be transmitted as efficiently as the wild-type virus in ferrets (15). This finding contrasted with previous observations that A/Sydney/5/97-like (H3N2) influenza virus with the R292K NA mutation was not transmissible under conditions in which the wild-type virus was efficiently transmitted (14) and that A/New Caledonia/20/99-like (H1N1) virus with the H274Y NA mutation required a challenge dose 100 times higher and was less transmissible than the wild-type virus (14).
~
Webster/Hoffman LaRoche appear to have forecast the result obtained in the 2007-08 influenza season, although transmission efficiency results were not quite in line with reality.
I think the Tamiflu makers were well aware that these strains would give rise to drug resistant mutants. Nobody said peep-one that they were integral to years of commercial influenza vaccines, however, since it would result in a hard hit to drug sales (which had been flagging anyway, due to cautionary reports of child/adolescent drug neurological side effects, 2006-07 out of Japan and hit-ir-miss protection against seasonal influenza).
Far as I can tell, the influenza vaccine and antiviral drug industry set up conditions ripe for widespread resistance.
